AIDS-associated lymphoma has a poor prognosis. Although in a subpopulation of patients the lymphoma appears to be arrested with chemotherapy, in others infections in the setting of increased immunosuppression and myelosuppression may be fatal. Clearly less toxic alternative treatment approaches are needed. Monoclonal antibody (mAb) therapy is one such approach. Antitumor activity with minimal toxicity has been demonstrated here with 131-I-labeled OKB7, an IgG2b reactive with CD21, the EBV receptor, in B cell lymphomas not associated with AIDS. Peripheral blood B cells counts are depressed while T cells levels are maintained with OKB7 treatment. This may limit further T cell suppression in AIDS patients. Twenty to 25 patients will be treated with OKB7 labeled with 200 mCi of 13I-I in 4 divided doses. mAb R24 is an IgG3, reactive with the cell membrane ganglioside GD-3, which fixes human complement and mediates cytotoxicity. Tumor responses have been documented here against malignant melanoma, and studies are in progress with patients with Hodgkin's disease, T cell lymphoma and thymoma. Twelve to 20 patients with Hodgkin's disease and HIV infection will be treated with escalating doses of R24. JD118 is a complement-fixing IgM with highly restricted reactivity with normal and malignant B cells. It will be potentially active in unconjugated form in. B cell lymphoma. Like R24 it is unlikely to be myelosuppressive or toxic to T cells. Twelve to 20 patients with AIDS-associated B cell lymphomas will be treated with escalating doses of antibody. Ancillary laboratory studies will also be performed. Quantitative studies of retroviral load and production are necessary parameters of toxicity and may indicate the most effective way of combining mAb and antiretroviral therapy in the future. Serum and cellular markers will permit monitoring of AIDS activity. Serial cytogenetic studies and molecular biological studies, in particular of the breakpoints for MYC in these patients,may give further insights into the biology of AIDS-related B cell lymphomas.